Peripheral nerve hyperexcitability (PNH) typically presents with complaints of muscle twitching, cramps, and muscle stiffness. Symptoms and signs indicating central and/or autonomic nervous system dysfunction also may be reported. An electroclinical spectrum exists, spanning from the milder cramp-fasciculation syndrome to more severe syndromes characterized by continuous muscle fiber activity. It is important to recognize that PNH may be an autoimmune phenomenon associated with antibodies targeting proteins of the voltage-gated potassium channel–complex and, in some patients, a paraneoplastic phenomenon. Symptomatic therapies include medicines that reduce neuronal excitability and in severe disease immunomodulatory treatments may be indicated.